title: Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib.
abstract: BACKGROUND
  This prospective, phase II trial evaluated the efficacy and safety of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours (GISTs) after failure of at least imatinib and sunitinib.
  
  
  METHODS
  Patients received oral dovitinib, 500 mg once daily, for 5 consecutive days, followed by a 2-day rest, every 28 days. The primary endpoint was disease control rate (DCR; objective response+stable disease (SD)) at 24 weeks, assessed by computed tomography (CT) scan according to RECIST v1.0. Metabolic response was evaluated by positron emission tomography (PET)-CT scans performed at baseline and after 4 weeks of treatment.
  
  
  RESULTS
  Between September 2011 and April 2012, 30 patients were enrolled. DCR at 24 weeks by RECIST v1.0 was 13% and one patient (3%) had a partial response. Based on the European Organization for Research and Treatment of Cancer PET response criteria, four patients (13%) had a metabolic partial response after 4 weeks of treatment. At a median follow-up of 8.3 months (range, 6.3-12.2 months), median progression-free survival (PFS) was 3.6 months (95% confidence interval (CI), 3.5-3.7 months) and median overall survival was 9.7 months (95% CI, 6.0-13.4 months). Metabolic progressive disease at Week 4 was significantly associated with shorter PFS (P=0.03). Grade 3/4 adverse events included asthenia (20%), neutropenia (13%), thrombocytopenia (10%), and hypertriglyceridaemia (10%). Most toxicities were manageable by dose modification.
  
  
  CONCLUSIONS
  Dovitinib showed modest antitumour activity with manageable toxicities in heavily pretreated patients with advanced GISTs.
authors.affiliation: Department of Oncology and Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Kang
authors.forename: C
authors.initials: C
authors.lastname: Yoo
authors.forename: B-Y
authors.initials: BY
authors.lastname: Ryoo
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Tan
authors.forename: I
authors.initials: I
authors.lastname: Park
authors.forename: J H
authors.initials: JH
authors.lastname: Park
authors.forename: Y J
authors.initials: YJ
authors.lastname: Choi
authors.forename: J
authors.initials: J
authors.lastname: Jo
authors.forename: J-S
authors.initials: JS
authors.lastname: Ryu
authors.forename: M-H
authors.initials: MH
authors.lastname: Ryu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077210:Sunitinib
chemical_list: C500007:4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; D000970:Antineoplastic Agents; D001549:Benzamides; D001562:Benzimidazoles; D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D015363:Quinolones; D000068877:Imatinib Mesylate; D000077210:Sunitinib